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The HIV-1 gag precursor is processed via two pathways: implications for cytotoxicity
1Department of Medicine, University of North Carolina, Chapel Hill 27599-7295.
Biomedica Biochimica Acta
|January 1, 1991
Summary
Human immunodeficiency virus type 1 (HIV-1) Gag precursor processing occurs via two pathways, one yielding virions and another accumulating cytoplasmic proteins. Cytoplasmic processing correlates with cell killing, indicating protease toxicity.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Retroviruses, including HIV-1, possess proteases essential for processing viral precursor proteins.
- These proteases liberate structural and enzymatic proteins required for viral capsid formation.
Purpose of the Study:
- To investigate the processing pathways of the Human Immunodeficiency Virus type 1 (HIV-1) Gag precursor.
- To determine the role of cytoplasmic Gag processing in viral pathogenesis and cell toxicity.
Main Methods:
- Analysis of HIV-1 Gag precursor processing in infected cells.
- Comparison of cytoplasmic processing in lytically infected versus non-lytic cells.
Main Results:
- HIV-1 Gag precursor is processed through both a membrane-associated pathway (producing virions) and a cytoplasmic pathway.
- Accumulation of processed viral proteins in the cytoplasm was observed via the cytoplasmic pathway.
- A strong correlation exists between the extent of cytoplasmic processing and cell killing.
Conclusions:
- The HIV-1 protease can process Gag precursors in the cytoplasm, independent of virion formation.
- Cytoplasmic accumulation of processed viral proteins suggests a mechanism for protease-induced cellular toxicity.
- Cytoplasmic processing is linked to the cytopathic effects of HIV-1 infection.